Two ACTive (TACTI): Results of a Phase I Trial With Metastatic Melanoma Patients (TACTI-mel) Treated With a Soluble LAG-3 Receptor (LAG-3lg Or ) as an Presenting Cell (APC) Activator Combined with

Frédéric Triebel MD, PhD ICI Europe Berlin, November 28, 2018 Notice: Forward Looking Statements

The purpose of the presentation is to provide an update of the business of Limited ACN 009 237 889 (ASX:IMM; NASDAQ:IMMP). These slides have been prepared as a presentation aid only and the information they contain may require further explanation and/or clarification. Accordingly, these slides and the information they contain should be read in conjunction with past and future announcements made by Immutep and should not be relied upon as an independent source of information. Please refer to the Company's website and/or the Company’s filings to the ASX and SEC for further information.

The views expressed in this presentation contain information derived from publicly available sources that have not been independently verified. No representation or warranty is made as to the accuracy, completeness or reliability of the information. Any forward looking statements in this presentation have been prepared on the basis of a number of assumptions which may prove incorrect and the current intentions, plans, expectations and beliefs about future events are subject to risks, uncertainties and other factors, many of which are outside Immutep’s control. Important factors that could cause actual results to differ materially from assumptions or expectations expressed or implied in this presentation include known and unknown risks. Because actual results could differ materially to assumptions made and Immutep’s current intentions, plans, expectations and beliefs about the future, you are urged to view all forward looking statements contained in this presentation with caution. Additionally, the INSIGHT investigator sponsored clinical trial described in this presentation is controlled by the lead investigator and therefore Immutep has no control over this clinical trial. This presentation should not be relied on as a recommendation or forecast by Immutep. Nothing in this presentation should be construed as either an offer to sell or a solicitation of an offer to buy or sell shares in any jurisdiction.

2 Timeline of discovery.

3 LAG-3 as a Therapeutic Target

• LAG-3 is widely expressed on tumor infiltrating lymphocytes (TILs) and cytotoxic T cells  Prime target for an immune checkpoint blocker • Functionally similar to PD-1 on T cells (arrow on the right)

 Positive LAG-3/ MHC class II interaction regulation of antigen presenting cells (APC)  increase in antigen presentation to cytotoxic CD8+ T cells  Negative regulation of LAG-3+ T cells

4 Targeting LAG-3/MHC II May Lead to Multiple Therapeutics in Numerous Indications

IMMUNOSTIMULATION IMMUNOSUPPRESSION

IMP321

APC Activator APC Agonistic mAb IMP761

MHCII Depleting LAG-3 mAb Antagonistic Partnered with mAb Partnered with LAG-3 IMP701 T-Cell T-Cell IMP731

Rheumatoid IBD Multiple Sclerosis Immuno-oncology Viral Infections Arthritis Combination Therapies

5 Increasing Clinical Trials Targeting LAG-3

Industry increasingly deploying resources to development of LAG-3 therapeutics

40 38 12,000

35 10,000 Patients Total in Estimated LAG 30 10,243 8,000 25 20 3 Clinical Trials Clinical 3 - 20 6,000 14 15

5,630 - 4,000 Trials 3 7 NumberLAG of 10 4 4,754 2,000 5 1 2,895 1,539 0 1,000 0 2013 2014 2015 2016 2017 2018 Total Est. Patients* No. Clinical Trials*

Sources: GlobalData, company websites, clinical trials.gov, and sec.gov Information as of August 17, 2018 6 *2018 includes planned and completed trials, includes trials where the company may not be the sponsor Lead Program Eftilagimod Alpha (IMP321) Eftilagimod alpha (IMP321) Soluble dimeric recombinant form of LAG-3Ig (fusion protein) VL D4 D2 D1 VH CL D3 CH1 Soluble LAG-3 Hinge CH2 MHC II binding site CH3 D1 Human IgG1 IMP321 “LAG-3Ig” D2 D3

D4 Hinge

CH2

CH3

• Soluble recombinant form of LAG-3 • Human fusion protein • Dimeric, very stable, high affinity for DC • Antigen presenting cell (APC) activator • Unique and first-in-class

8 IO Therapy Oncology Response Rates

Approximately 70-80% of patients do no respond to anti-PD1 monotherapy. How can we enable more efficacious T-cell responses?

• Immunogenic cell death to liberate/uncover tumor • Cross-presentation of those antigens • Recruitment of T cells into the tumor microenvironment • Reversing the pathways driving a repressive tumor environment This could be achieved through the right APC activation

APC activators: • MHC II agonism • TLR or STING agonism • CD40 agonism • Oncolytic viral therapies

9 eftilagimod alpha (IMP321): an APC activator (i.e. not an ICI)

“PUSHING THE ACCELERATOR ON IMMUNE RESPONSES” “RELEASING THE BRAKE ON THE ”

eftilagimod alpha: • MHC II agonist eftilagimod alpha (efti, IMP321): LAG-3 antagonist antibodies: • LAG-3 fusion protein APC activator Immune checkpoint inhibitor (ICI) • Boost and sustain the CD8+ T cell responses • increase cytotoxicity of the pre-existing CD8 T • Activate multiple immune cell subsets cell response

10 Rationale for Combining efti (IMP321) with or Anti-PD-1 mAb

Therapeutic interventions leading to increased T cell responses in . The Cancer Immunity Cycle. Adapted from Chen and Mellman (1).

11 Combining eftilagimod alpha and first-line single agent chemotherapy Eftilagimod alpha in MBC Active (AIPAC, Pivotal Phase IIb)

Arm 1, 113 patients: Safety-run in, paclitaxel + IMP321 Phase IIb, Safety Run-in: recommended 15 (6+9) patients, Stage 2 multinational, Phase IIb dose (RP2D) Stage randomized, double- 2 cohorts Arm 2, 113 patients: 2: Efficacy (PFS) blind paclitaxel + placebo

Primary Run-In: Recommended Phase II dose (RP2D) Status report (Nov 2018) Objective Stage 2: Efficacy (PFS) of paclitaxel + IMP321 vs. ✓ Safety run-in completed successfully paclitaxel + placebo ✓ Randomized phase started early 2017 with the RP2D Other Anti-tumor activity, safety and tolerability, (30 mg) Objectives pharmacokinetic and immunogenic properties, quality of life of IMP321 plus paclitaxel compared to placebo ✓ Interim-data of safety run-in presented at ASCO 2017 Patient Advanced MBC indicated to receive 1st line weekly ✓ To-date, efficacy and safety data in-line with Population paclitaxel historical control group/ prior clinical trials (Brignone et al Journal Translational Medicine 2010, Treatment Run-in: IMP321 (6 or 30 mg) + Paclitaxel 8:71) Arm 1: Paclitaxel + IMP321 (30 mg) ✓ >160 patients recruited in Stage 2 Arm 2: Paclitaxel + Placebo Countries NL, BE, PL, DE, HU, UK, FR → overall 30+ sites

13 Eftilagimod alpha in MBC Preliminary Efficacy Results

Observed response rates are substantially better than the 22-33% response rates seen in historical control groups with paclitaxel monotherapy

Phase I (n=30) AIPAC – Safety Run Phase (n=15) Response Parameter Paclitaxel + IMP321 (n = 15) Complete Response (CR) 0/15 (0%) Partial Response (PR) 7/15 (47%) Stable Disease (SD) 6/15 (40%) Progressive Disease (PD) 2/15 (13%) Overall Response Rate (ORR) 7/15 (47%)

Disease Control Rate (DCR) 13/15 (87%) • ORR* of 47% and DCR** of 83% • ORR of 47% and DCR of 87% • Responders had further tumor • Two of the responses occurred shrinkage between months 3 and 6 relatively late (after ~6 months)

*Overall Response Rate **Disease Control Rate Preliminary data, status Interim CSR April 2018, best response acc. To RECIST 1.1

14 AIPAC Immunomonitoring Primary Target Cells

Primary target cells: Sustained increase of circulating Antigen- Presenting Cells (APCs) like (A) and dendritic cells (B). Rapid activation of monocytes (CD16 (C) and CD40 (D)).

15 AIPAC Immunomonitoring Secondary Target Cells

Secondary target cells: Sustainable increase in absolute numbers of effector cells like i.e. CD8 T cells (A) and Natural Killer cells (B). IMP321 induces early and sustainable increase of Th1 biomarkers like IFN-g (C) and IP-10 (CXCL10, D).

16 Combining eftilagimod alpha and pembrolizumab New Rationale for Combining eftilagimod alpha (IMP321) with PD-1 Antagonists (pembrolizumab)

IMP321 increases number in cancer patients  Baseline innate immunity status seems to be important for the response (OS) to pembrolizumab  Data suggests that low monocyte numbers at baseline are associated with poor efficacy of anti-PD-1 therapy in melanoma patients

N=51  Data shows that the APC activator eftilagimod alpha boosts innate immunity Source: Krieg et al., Nat. Med. 24, 2018.

18 TACTI-mel: Two ACTive Immunotherapies (melanoma)

Study Scheme Part A:

• 18 pts in total  6 pts per efti dose group • Patients received: o 2 mg/kg pembrolizumab i.v. every 3 weeks o 1, 6, 30 mg efti s.c. every 2 weeks for up to 6 months • Imaging was done every 12 weeks

* - tumor assessments done acc. to irRC irRC…Immune-Related Response Criteria, PFS- 19 progression free survival, FU – follow-up TACTI-mel Part A: Safety Summary

Overview grade 3 / 4 TEAEs and rel. to study treatment Overview frequent TEAE (PT selected if ≥ 10 % of the pts) Grade 3 Grade 4 Preferred term Rel to efti / Adverse Any grade Grade 3 or 4 No of N (%) N (%) pembro Event*, N (%) N (%) events

Maculo-papular rash 1 (6 %) - No/ Yes Arthralgia 3 (17) - 3

Decreased renal function 1 (6 %) - Yes / No Diarrhea 5 (28) - 6 Fatigue 8 (44) - 10 Colitis 1 (6 %) - No/ Yes Hyperglycemia 3 (17) 3 (17) 3 Altered liver functions 1 (6 %) - No/ Yes Nausea 5 (28) - 7

• No Dose limiting toxicities observed Rash## 7 (39) 1 (6) 7

• 6 pts (33 %) with ≥ 1 SAE; none related to any study drug Adverse events occurred in > % 10of pts * - rash of kind any ## - • 8 pts (44 %) with ≥ 1 AE with ≥ grade 3 (no grade 5) • No new safety signals • 1 pt died due to an AE (grade 4 Intercranial hemorrhage, not rel.) • 1 pt discontinued due to an AE (not rel.) • 3 pts experienced treatment delay due to an AE

20 preliminary data, status Oct 15th 2018 TACTI-mel Part A: Baseline Characteristics + Efficacy Summary Baseline Characteristics N = 18 (%) Best Overall Response acc. to irRC N = 18 (%) Age (median) 67 yrs irCR 1 (6 %)

Sex (f/m) 1 (6 %) / 17 (94 %) irPR# 5 (28 %)#

Elevated LDH 7 (39%) irSD 6 (33 %)

Metastasis stage M1c 14 (78 %) irPD 6 (33 %)

Pre-treated with 5 (28 %) Best overall response rate (ORR) 6 (33 %) BRAF/MEK/ipilimumab Patients with tumor shrinkage 10 (56 %)

irPD/irSD to pembro after 3 11 (61 %) Disease control rate 12 (66 %) cycles # - incl. 1 pt with complete disappearance of all target lesions • Very late stage of disease (M1c, elevated LDH) and majority not responding to • If response is calculated from pre- pembrolizumab monotherapy pembro timepoint  ORR is 61 % acc. to irRC

21 preliminary data, status Oct 15th 2018 TACTI-mel Part A: Response patterns

Spiderplot* Cohort 1-3 TACTImel TACTI-mel 800 waterfall plot (irRC) 400 irPD 600 300 irPD 100 irSD irSD 100 irPR irPR irCR 50 irCR 50 0 0 -50 n =18 -50 % % change from baseline -100 -100 pre- 0 3 6 9 12 15 18 21 24 27 % % changecompared tostartofcombo pembro start of combo months * - acc to irRC

 Tumor shrinkage in 10 (56 %) of these patients  1 pt with confirmed CR + 4 pts still on Tx after 12 months incl. 2 pts with complete disappearance of all  5 (28 %) pts with long term (>12 mths) treatment/benefit target lesions

preliminary data, status Oct 15th 2018 22 TACTI-mel Part A): Single Case

• 84 year old male with multiple lung metastases from melanoma • BRAF wild type

Tumor progression

• Patient progressing on pembrolizumab monotherapy • At 1 yr all lesions disappeared  CR (confirmed) • Patient without treatment and disease free  now lost to FU

preliminary data, status Oct 15th 2018 23 TACTI-mel Part B: Preliminary results

Study Scheme Part B: Study Status & Results part B:

• Recruitment and safety observation period completed • 5 pts had at least 1 post baseline CT

Baseline Characteristics N = 6 Age (median) 65 yrs Sex (f/m) 1 (13 %) / 5 (83 %) ECOG (0/1) 3 (50 %) / 3 (50 %) Details: Elevated LDH 5 (83%) • 6 pts enrolled Stage M1c 6 (100 %) • Patients received: o 2 mg/kg pembrolizumab i.v. every 3 weeks • No DLTs or new safety signals detected o 30 mg efti s.c. every 2 weeks for up to 12 months • • Imaging was done every 12 weeks 3 / 5 evaluable pts (60 %) had irPR at 3 months • 4 pts still under treatment (1 pt died due to PD < 3 months, 1 pt left with confirmed irPD)

* - tumor assessments done acc. to irRC irRC…Immune-Related Response Criteria, PFS- 24 progression free survival, FU – follow-up TACTI-002 Trial Design

An umbrella trial: Two ACTive Immunotherapeutics in different indications

Efti (IMP321) + Pembrolizumab Phase II, multi- Simon’s 2 stage; 3 Response rate; PFS, OS, PK, (Keytruda) for 12 months + max. national (EU + US indications; up to 120 Biomarker; Safety and of 12 months pembrolizumab + AUS), open pts tolerability monotherapy label

Primary Response rate (iRECIST) Objective Other Objectives Safety, PFS+OS, PK, exploratory biomarker analysis Patient Part A: 1st line NSCLC PD-X naive Population Part B: 2nd line NSCLC, PD-X refractory Part C: 2nd line HNSCC, PD-X naive

Treatment 30 mg Efti (IMP321) s.c. 200 mg Pembrolizumab i.v. 13 sites in Europe / US / Australia

Notes data monitoring comittee, PFS – progression free survival, OS – overall survival, PK – NSCLC – non-small-cell lung cancer, HNSCC – head and neck squamous cell cancer, DMC – pharmacokinetics, PD-X – any PD-1 or PDL-1 treatment 25 Thank you

Frédéric Triebel MD, PhD ICI Europe Berlin, November 28, 2018